芹菜素对2型糖尿病合并非酒精性脂肪肝小鼠脂代谢紊乱的作用及机制研究  

Effects and mechanisms of apigenin on lipid metabolism disorder in mice with type 2 diabetes combined with nonalcoholic fatty liver disease

作　　者：候丹 许光远 吴丽丽[1] 刘铜华[1] HOU Dan;XU Guangyuan;WU Lili;LIU Tonghua(Beijing Key Laboratory of Health Preservation of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Chinese Medicine,Fuxing Hospital Affiliated to Capital Medical University,Beijing 100045,China)

机构地区：[1]北京中医药大学中医养生学北京市重点实验室,北京100029 [2]首都医科大学附属复兴医院中医科,北京100045

出　　处：《上海中医药杂志》2018年第11期64-68,共5页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家"十二五"科技支撑计划项目(2014BAI10B04)

摘　　要：目的研究芹菜素对2型糖尿病合并非酒精性脂肪肝小鼠脂代谢紊乱的作用及机制。方法 8周龄雄性db/db小鼠随机分组分为模型组、芹菜素组(50 mg·kg^(-1)·d^(-1)),以雄性C57BL/6J小鼠为正常对照组。各干预8周后,检测小鼠体质量、空腹血糖(FBG)、总胆固醇(CHO)、三酰甘油(TG)、游离脂肪酸(FFA)、天门冬氨酸氨基转移酶(AST)、成纤维细胞生长因子-19(FGF-19)、空腹胰岛素水平(Fins)和胰岛素抵抗指数(HOMA-IR);肝组织HE染色观察肝细胞脂质蓄积; RT-PCR检测肝脏SREBP1c、FAS、Sirt1、PGC1α、CPT1基因表达; Western blot检测PPARα蛋白表达。结果与模型组比较,芹菜素组小鼠体质量、FBG、CHO、TG、FFA显著降低(P<0.05,P<0.01),FGF-19显著升高(P<0.01); HE染色肝细胞脂肪变性程度减轻,胞内脂滴数量减少,细胞排列整齐;肝脏SREBP1c、FAS mRNA表达降低(P<0.05,P<0.01),Sirt1、PGC1α、CPT1αmRNA表达显著升高(P<0.05); PPARα蛋白表达显著升高(P<0.01)。结论芹菜素可以改善糖尿病合并非酒精性脂肪肝小鼠肝脏脂肪代谢紊乱,可能是通过下调肝脏SREBP1c、FAS mRNA表达,上调肝脏Sirt1、PGC1α、CPT1α、PPARα表达实现的。Objective To investigate the effects and mechanisms of apigenin on lipid metabolism disorder in mice with type 2 diabetes combined with nonalcoholic fatty liver disease( NAFLD). Methods 8-week old male db/db mice were randomly divided into the model group and apigenin group( 50 mg·kg^-1·d^-1). Male C57 BL/6 J mice were taken as the normal control group. After drug treatment for 8 weeks,the body weight,fasting blood glucose( FBG),total cholesterol( CHO),triglyceride( TG),free fatty acid( FFA),aspartate aminotransferase( AST),fibroblast growth factor-19( FGF-19),fasting insulin( Fins) and homeostasis model assessment of insulin resistance( HOMA-IR) of mice were detected. HE staining was performed in liver tissue to observe the lipid deposition in hepatocytes. The m RNA expressions of SREBP1 c,FAS,Sirt1,PGC1α and CPT1 were detected by RT-PCR and the protein expression of PPARα was detected by Western blot. Results Compared with the model group,the body weight and levels of FBG,CHO,TG and FFA in the apigenin group were decreased significantly( P<0.05,P<0.01),and the FGF-19 level was increased significantly( P<0.01). HE staining showed that the degree of lipid deposition in hepatocytes was alleviated,the number of intracellular lipid droplets was reduced and the cells arranged regularly in the apigenin group. The m RNA expressions of SREBP1 c and FAS in liver were decreased( P<0.05,P<0.01),the m RNA expressions of Sirt1,PGC1α and CPT1α were significantly increased( P<0.05),and the protein expression of PPARα was significantly increased( P<0.01) in the apigenin group. Conclusion Apigenin can improve the liver lipid metabolism disorder in mice with diabetes combined with NAFLD,which may be accomplished by down-regulating the m RNA expressions of SREBP1 c and FAS and up-regulating the expressions of Sirt1,PGC1α,CPT1α and PPARα in liver.

关 键 词：2型糖尿病 非酒精性脂肪肝 芹菜素 脂代谢 小鼠 

分 类 号：R285.5[医药卫生—中药学]